By Jeffrey Zimmet, MD, PhD

Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center

Dr. Zimmet reports no financial relationships relevant to this field of study.

SYNOPSIS: In a small randomized trial of patients with cardiogenic shock secondary to acute myocardial infarction, the Impella heart pump failed to improve mortality compared with intra-aortic balloon counterpulsation.

SOURCE: Ouweneel DM, Eriksen E, Sjauw KD, et al. Percutaneous mechanical circulatory support versus intra-aortic balloon pump in cardiogenic shock after acute myocardial infarction. J Am Coll Cardiol 2017;69:278-287.

Despite major advances in coronary revascularization techniques and medical therapy, mortality rates for cardiogenic shock complicating acute myocardial infarction have not changed substantially over more than a decade. Indeed, 30-day mortality in the original SHOCK trial (published in 1999) averaged approximately 50%, and this remains a fairly accurate estimate today. The failure of intra-aortic balloon counterpulsation to change mortality in the 2012 IABP-SHOCK II trial has led to increased interest in potentially more effective mechanical support devices.

The Impella device is a minimally invasive ventricular support device that sits across the aortic valve, resting in the left ventricle and providing positive forward flow. The currently available Impella CP has a maximum output of 3.7 L/minute, and in most cases can be inserted from the femoral arterial approach. Prior trials have demonstrated that the Impella can be implanted safely in cardiogenic shock patients and that it gives significantly greater levels of hemodynamic support compared with the intra-aortic balloon pump (IABP). Earlier trials primarily were conducted using the less-powerful Impella 2.5 system and did not target mortality as an outcome measure.

The IMPella versus IABP Reduces mortality in STEMI patients treated with primary PCI in Severe cardiogenic SHOCK (IMPRESS) trial randomized patients with severe cardiogenic shock due to ST-segment elevation myocardial infarction to treatment with either IABP or the Impella CP device. This was a modest-sized trial and was intended to be enriched for very sick patients. To that end, only mechanically ventilated patients were included. Among the 48 patients included in the trial, 44 (92%) had suffered cardiac arrest before randomization. All patients received pressor medications, 31% received renal replacement therapy, and 75% were treated with therapeutic hypothermia.

Twenty-four patients were randomized to each group. The infarct-related artery was the left anterior descending (LAD) in 65% of patients, and 98% were revascularized successfully by percutaneous coronary intervention with stenting. The majority of patients received the assigned mchanical support. At 30 days, mortality was not significantly different between the two groups: 50% with IABP, and 46% in the Impella group (hazard ratio, 0.96; 95% confidence interval, 0.42-2.18; P = 0.92). Mortality at six months was 50% in each group.

The authors termed this an “explorative” randomized trial and concluded that routine use of mechanical circulatory support in patients with severe cardiogenic shock did not improve survival, compared with IABP.

COMMENTARY

“Explorative” is an interesting choice of words to use in a paper’s conclusion, and it is worthwhile for a moment to delve into what this means. First, this was a small trial, with only 24 patients per group. To select a group with high mortality, and to increase the odds that the intervention would be able to significantly change outcomes, the investigators selected only patients who were intubated, and included primarily patients who had been resuscitated from cardiac arrest. The power calculation assumed a baseline 30-day mortality of 95% in the IABP group, which, of course, turned out to be unrealistic. However, the predictable result was the selection of a significant number of patients who had no genuine opportunity to be salvaged. Indeed, the cause of death in nearly half of patients was listed as anoxic brain injury, while only 29% died due to refractory cardiogenic shock or multi-organ failure. Although inclusion of such post-resuscitation, brain-damaged patients “resembles a real-life cohort,” in the words of the authors, it does not provide much of an opportunity to demonstrate a survival advantage from a mechanical support device.

This trial highlights some disadvantages of using the Impella device. For example, bleeding was more frequent with the Impella (33% of patients) compared with IABP, and this is logical given the relatively large vascular access required (14F) and the need for continued heparin anticoagulation while the device is in place. Hemolysis was noted in 8%, which is comparable to prior reports of the device. The issue of cost is not discussed, but at more than $25,000 per catheter, it cannot be ignored, especially in the absence of a positive outcome.

So what are we to learn from these new data? Cardiogenic shock remains a major scourge, with high mortality and few proven therapies beyond percutaneous revascularization. Although mechanical circulatory support with devices like the Impella holds intuitive appeal for treatment of these patients, for now we are left without supporting data. Ultimately, larger trials with more careful patient selection will be needed to answer this question with any certainty.